Downregulation of PGC-1α during cisplatin-induced muscle atrophy in murine skeletal muscle

Ken Sato; Yoshida Satoshi; Yu Miyauchi; Fumiaki Sato; Risako Kon; Nobutomo Ikarashi; Yoshihiko Chiba; Tomoo Hosoe; Hiroyasu Sakai

doi:10.1016/j.bbadis.2023.166877

Downregulation of PGC-1α during cisplatin-induced muscle atrophy in murine skeletal muscle

Biochim Biophys Acta Mol Basis Dis. 2024 Jan;1870(1):166877. doi: 10.1016/j.bbadis.2023.166877. Epub 2023 Sep 4.

Authors

Ken Sato¹, Yoshida Satoshi¹, Yu Miyauchi¹, Fumiaki Sato², Risako Kon¹, Nobutomo Ikarashi¹, Yoshihiko Chiba³, Tomoo Hosoe⁴, Hiroyasu Sakai⁵

Affiliations

¹ Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan.
² Department of Analytical Pathophysiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan.
³ Department of Physiology and Molecular Sciences, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan.
⁴ Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan; Department of Bioregulatory Science, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan.
⁵ Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan. Electronic address: sakai@hoshi.ac.jp.

PMID: 37673360
DOI: 10.1016/j.bbadis.2023.166877

Abstract

This study aimed to investigate the effects of cisplatin on adenosine triphosphate (ATP) levels, expressions of genes related to mitochondrial oxidative phosphorylation (OXPHOS), and the factors related to mitochondrial biosynthesis in skeletal muscle. Systemic cisplatin administration decreased skeletal muscle mass, skeletal muscle strength, and endurance. The mitochondrial DNA /nuclear DNA ratio was also reduced after treatment with cisplatin. Moreover, among the factors related to mitochondrial biogenesis and function, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) was significantly downregulated in the cisplatin-treated group. Downregulation of PGC-1α in the skeletal muscle may contribute to muscle weakness during cisplatin-induced muscle atrophy.

Keywords: ATP; Cisplatin; Mitochondria; Muscle atrophy; PGC-1α.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cisplatin* / adverse effects
DNA, Mitochondrial / metabolism
Down-Regulation
Mice
Muscle, Skeletal / metabolism
Muscular Atrophy / chemically induced
Muscular Atrophy / genetics
Muscular Atrophy / metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
Transcription Factors* / genetics
Transcription Factors* / metabolism

Substances

Cisplatin
Transcription Factors
DNA, Mitochondrial
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha